Comparative Genomics of the BDNF Gene, Non-Canonical Modes of Transcriptional Regulation, and Neurological Disease

Alternative splicing of genes in the central nervous system is ubiquitous and utilizes many different mechanisms. Splicing generates unique transcript or protein isoforms of the primary gene that result in shortened, lengthened, or reorganized products that may have distinct functions from the paren...

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Bibliographic Details
Published in:Molecular neurobiology 2021-06, Vol.58 (6), p.2851-2861
Main Author: Keifer, Joyce
Format: Article
Language:English
Subjects:
Alternative splicing
Biomedical and Life Sciences
Biomedicine
Brain-derived neurotrophic factor
Cell Biology
Central nervous system
Environmental effects
External stimuli
Gene regulation
Genes
Genomics
Isoforms
Neurobiology
Neurological diseases
Neurology
Neurosciences
Synaptic plasticity
Synaptogenesis
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Summary:Alternative splicing of genes in the central nervous system is ubiquitous and utilizes many different mechanisms. Splicing generates unique transcript or protein isoforms of the primary gene that result in shortened, lengthened, or reorganized products that may have distinct functions from the parent gene. Learning and memory genes respond selectively to a variety of environmental stimuli and have evolved a number of complex mechanisms for transcriptional regulation to act rapidly and flexibly to environmental demands. Their patterns of expression, however, are incompletely understood. Many activity-inducible genes generate transcripts by alternative splicing that have an unknown physiological or behavioral function. One such gene codes for the protein brain-derived neurotrophic factor (BDNF). BDNF is a neurotrophin whose expression is essential for cellular growth, synaptogenesis, and synaptic plasticity. It is an important model gene because of its complex structure and the variety of transcriptional mechanisms it displays for expression in response to external stimuli. Some of these are unexpected, or non-canonical, transcriptional control mechanisms that require further exploration in an activity-dependent context. In this review, a comparative genomics approach is taken to highlight the different forms of BDNF gene transcription including potential autoregulatory mechanisms. Modes of BDNF control have general implications for understanding the origins of several neurological disorders that are associated with reduced BDNF function.
ISSN:0893-7648
1559-1182
DOI:10.1007/s12035-021-02306-z